Neisseria meningitidis (meningococcus) is a Gram negative human pathogen. It colonizes the pharynx, causing meningitis and, occasionally, septicemia in the absence of meningitis. It is closely related to N. gonorrhoeae, although one feature that clearly differentiates meningococcus is the presence of a polysaccharide capsule that is present in all pathogenic meningococci.
Based on the organism's capsular polysaccharide, twelve serogroups of N meningitidis have been identified (A, B, C, H, I, K, L, 29E, W135, X, Y and Z). Group A is the pathogen most often implicated in epidemic disease in sub-Saharan Africa. Serogroups B and C are responsible for the vast majority of cases in USA and in most developed countries. Serogroups W135 and Y are responsible for the remaining cases in USA and developed countries.
A tetravalent vaccine of capsular polysaccharides from serogroups A, C, Y and W135 has been known for many years and has been licensed for human use. Although effective in adolescents and adults, it induces a poor immune response and short duration of protection and cannot be used in infants. This is because polysaccharides are T cell-independent antigens that induce a weak immune response that cannot be boosted. The polysaccharides in this vaccine are not conjugated and are present at a 1:1:1:1 ratio. MENCEVAX ACWY™ contains 50 μg of each purified polysaccharide once reconstituted from its lyophilized form.
Conjugate vaccines against serogroup C have been approved for human use, and include MENJUGATE™, MENINGITEC™ and NEISVAC-C™. Mixtures of conjugates from serogroups A+C+W135+Y have also been approved for human use, and include MENVEO™ and MENACTRA™.
With the proliferation of meningococcal capsular saccharide vaccines, there is a need for methods of assessing the immunogenicity, potency, or both, of each batch of vaccine after manufacture to ensure that each batch will produce the expected immune response without having to immunize a test animal with a sample from each such batch or rely upon mere physical characterization of the capsular saccharide components. Any such method must meet strict governmental regulatory requirements for release of a vaccine that are set by agencies such as the U.S. Food and Drug Administration (the FDA) in the United States and the European Medicines Agency (the EMEA) in Europe. Therefore correlates for immunogenicity, potency, or both that may work in a laboratory will not necessarily meet the requirements of regulatory agencies given that the vaccine will be administered to a human subject. It is therefore an object of the invention to provide methods for assessing immunogenicity, potency, or both, of meningococcal capsular saccharide vaccines that meet the exacting standards of governmental regulatory agencies by measuring binding to a bactericidal antibody specific for the capsular saccharide.